Evidence map›Paper›PMID 26142699›Full record

ArticlePflugers Archiv : European journal of physiology2016

Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate.

Rafael Jaimes, Sarah Kuzmiak-Glancy, Daina M Brooks, Luther M Swift, Nikki G Posnack, Matthew W Kay

Abstract read
In one paragraph

Article in Pflugers Archiv : European journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Rafael JaimesDepartment of Biomedical Engineering, The George Washington University, GWU Science and Engineering Hall, 800 22nd Street NW, Suite 5000, Washington, DC, 20052, USA.
Sarah Kuzmiak-GlancyDepartment of Biomedical Engineering, The George Washington University, GWU Science and Engineering Hall, 800 22nd Street NW, Suite 5000, Washington, DC, 20052, USA.
Daina M BrooksDepartment of Biomedical Engineering, The George Washington University, GWU Science and Engineering Hall, 800 22nd Street NW, Suite 5000, Washington, DC, 20052, USA.
Luther M SwiftDepartment of Pharmacology and Physiology, The George Washington University, Washington, DC, 20052, USA.
Nikki G PosnackDepartment of Pharmacology and Physiology, The George Washington University, Washington, DC, 20052, USA.
Matthew W KayDepartment of Biomedical Engineering, The George Washington University, GWU Science and Engineering Hall, 800 22nd Street NW, Suite 5000, Washington, DC, 20052, USA. phymwk@gwu.edu.
George Washington University · US

Funding

Low flow reperfusion after acute myocardial ischemia: when too little is too muchR01HL095828 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI KAY, MATTHEW W. · 2010 to 2014
$1.6M
The effect of endocrine disrupting chemicals on cardiac physiologyR00ES023477 · NIEHS · CHILDREN'S RESEARCH INSTITUTE · PI POSNACK, NIKKI GILLUM · 2016 to 2018
$740k
The effect of endocrine disrupting chemicals on cardiac physiologyK99ES023477 · NIEHS · GEORGE WASHINGTON UNIVERSITY · PI POSNACK, NIKKI GILLUM · 2014 to 2015
$210k
NHLBI NIH HHS HL095828NHLBI NIH HHS R01 HL095828NIEHS NIH HHS K99 ES023477NIEHS NIH HHS K99ES023477NIEHS NIH HHS R00 ES023477
6 · The paper itself

Abstract

Dichloroacetate (DCA) and pyruvate activate pyruvate dehydrogenase (PDH), a key enzyme that modulates glucose oxidation and mitochondrial NADH production. Both compounds improve recovery after ischemia in isolated hearts. However, the action of DCA and pyruvate in normoxic myocardium is incompletely understood. We measured the effect of DCA and pyruvate on contraction, mitochondrial redox state, and intracellular calcium cycling in isolated rat hearts during normoxic perfusion. Normalized epicardial NADH fluorescence (nNADH) and left ventricular developed pressure (LVDP) were measured before and after administering DCA (5 mM) or pyruvate (5 mM). Optical mapping of Rhod-2AM was used to measure cytosolic calcium kinetics. DCA maximally activated PDH, increasing the ratio of active to total PDH from 0.48 ± 0.03 to 1.03 ± 0.03. Pyruvate sub-maximally activated PDH to a ratio of 0.75 ± 0.02. DCA and pyruvate increased LVDP. When glucose was the only exogenous fuel, pyruvate increased nNADH by 21.4 ± 2.9 % while DCA reduced nNADH by 21.4 ± 6.1 % and elevated the incidence of premature ventricular contractions (PVCs). When lactate, pyruvate, and glucose were provided together as exogenous fuels, nNADH increased with DCA, indicating that PDH activation with glucose as the only exogenous fuel depletes PDH substrate. Calcium transient time-to-peak was shortened by DCA and pyruvate and SR calcium re-uptake was 30 % longer. DCA and pyruvate increased SR calcium load in myocyte monolayers. Overall, during normoxia when glucose is the only exogenous fuel, DCA elevates SR calcium, increases LVDP and contractility, and diminishes mitochondrial NADH. Administering DCA with plasma levels of lactate and pyruvate mitigates the drop in mitochondrial NADH and prevents PVCs.

Indexed as

Myocardial ContractionVentricular FunctionAnimalsCalciumDichloroacetic AcidGlucoseHeartIsolated Heart PreparationMyocardiumNADPyruvate Dehydrogenase ComplexPyruvic AcidRatsRats, Sprague-DawleyCalciumDichloroacetic AcidGlucoseNADPyruvate Dehydrogenase ComplexPyruvic AcidCardiacDichloroacetateNADHPyruvate dehydrogenase

Identifiers

PMID26142699
PMCPMC4701640
OpenAlexW789323051

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.